Inhaled nitric oxide (NO) is a selective pulmonary vasodilator. Uncontrolled clinical studies have suggested that inhaled NO improves oxygenation in patients with acute lung injury. Although controlled clinical studies evaluating the effectiveness of inhaled NO during acute lung injury have not been completed, this agent is being used with increasing frequency in European and U.S. hospitals. Inhaled NO has a number of potential toxicities that should be of great concern in patients presenting with acute lung injury related to pneumonia. Inhaled NO may aggravate oxidant lung injury via the formation of peroxynitrite and hydroxyl radical. Such injury might be amplified in patients with inflammatory lung injury on oxygen therapy. By down-regulating endothelial receptors for leukocyte adhesion and migration, NO also may limit important leukocyte host defense function during acute lung injury associated with infection. Studies evaluating the potential toxic long-term effects of inhaled NO during inflammatory lung injury associated with infection have not been conducted. We have developed the equipment and laboratory techniques necessary for long-term administration and monitoring of inhaled NO at varying levels of oxygen exposure in small animals. With these resources, we have started preliminary studies evaluating the effects of prolonged inhalation of NO in a rat model of Escherichia coli pneumonia at differing concentrations of oxygen. Although possibly worsening lung injury, NO did not worsen overall survival in these early studies. When laboratory renovations that temporarily stopped these studies are completed, studies will continue to assess the effects of inhaled NO on survival, oxidative lung injury, extravascular leukocyte recruitment, endothelial and epithelial leukocyte receptor expression, and bacterial clearance. Tissue receptor expression (ICAM-1 and P-selectin) are being conducted on tissues from this study by Dr. Steven Welti from Baylor University.